tbuckley/cabot-search huggingface dataset:
Ulcerative Colitis in Adults
Authors: Beatriz Gros, Gilaad G. Kaplan
Journal: JAMA (2023)

Importance Ulcerative colitis (UC) is a chronic inflammatory condition of the colon, with a prevalence exceeding 400 per 100 000 in North America. Individuals with UC have a lower life expectancy and are at increased risk for colectomy and colorectal cancer. Observations UC impairs quality of life secondary to inflammation of the colon causing chronic diarrhea and rectal bleeding. Extraintestinal manifestations, such as primary sclerosing cholangitis, occur in approximately 27% of patients with UC. People with UC require monitoring of symptoms and biomarkers of inflammation (eg, fecal calprotectin), and require colonoscopy at 8 years from diagnosis for surveillance of dysplasia. Risk stratification by disease location (eg, Montreal Classification) and disease activity (eg, Mayo Score) can guide management of UC. First-line therapy for induction and maintenance of remission of mild to moderate UC is 5-aminosalicylic acid. Moderate to severe UC may require oral corticosteroids for induction of remission as a bridge to medications that sustain remission (biologic monoclonal antibodies against tumor necrosis factor [eg, infliximab], α4β7 integrins [vedolizumab], and interleukin [IL] 12 and IL-23 [ustekinumab]) and oral small molecules that inhibit janus kinase (eg, tofacitinib) or modulate sphingosine-1-phosphate (ozanimod). Despite advances in medical therapies, the highest response to these treatments ranges from 30% to 60% in clinical trials. Within 5 years of diagnosis, approximately 20% of patients with UC are hospitalized and approximately 7% undergo colectomy. The risk of colorectal cancer after 20 years of disease duration is 4.5%, and people with UC have a 1.7-fold higher risk for colorectal cancer compared with the general population. Life expectancy in people with UC is approximately 80.5 years for females and 76.7 years for males, which is approximately 5 years shorter than people without UC. Conclusions and Relevance UC affects approximately 400 of every 100 000 people in North America. An effective treatment for mild to moderate UC is 5-aminosalicylic acid, whereas moderate to severe UC can be treated with advanced therapies that target specific inflammation pathways, including monoclonal antibodies to tumor necrosis factor, α4β7 integrins, and IL-12 and IL-23 cytokines, as well as oral small molecule therapies targeting janus kinase or sphingosine-1-phosphate.
Blood Levels of Organochlorine Contaminants Mixtures and Cardiovascular Disease
Authors: Carolina Donat-Vargas, Tessa Schillemans, Hannu Kiviranta, Panu Rantakokko, Ulf de Faire, Juan Pedro Arrebola, Alicja Wolk, Karin Leander, Agneta Åkesson
Journal: JAMA Network Open (2023)

Cardiovascular toxic effects derived from high exposures to individual organochlorine compounds are well documented. However, there is no evidence on low but continuous exposure to combined organochlorine compounds in the general population.To evaluate the association of combined exposure to several organochlorine compounds, including organochlorine pesticides and polychlorinated biphenyls, with incident cardiovascular disease (CVD) in the general population.This prospective nested case-control study included data from 2 cohorts: the Swedish Mammography Cohort-Clinical (SMC-C) and the Cohort of 60-Year-Olds (60YO), with matched case-control pairs based on age, sex, and sample date. Baseline blood sampling occurred from November 2003 to September 2009 (SMC-C) and from August 1997 to March 1999 (60YO), with follow-up through December 2017 (SMC-C) and December 2014 (60YO). Participants with myocardial infarction or ischemic stroke were matched with controls for composite CVD evaluation. Data were analyzed from September 2020 to May 2023.A total of 25 organochlorine compounds were measured in blood at baseline by gas chromatography-triple quadrupole mass spectrometry. For 7 compounds, more than 75% of the samples were lower than the limit of detection and not included.Incident cases of primary myocardial infarction and ischemic stroke were ascertained via linkage to the National Patient Register (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes I21 and I63). The quantile-based g-computation method was used to estimate the association between the combined exposure to several organochlorine compounds and composite CVD.Of 1528 included participants, 1024 (67.0%) were female, and the mean (SD) age was 72 (7.0) years in the SMC-C and 61 (0.1) years in the 60YO. The odds ratio of composite CVD was 1.71 (95% CI, 1.11-2.64) per 1-quartile increment of total organochlorine compounds mixture. Organochlorinated pesticides were the largest contributors, and β-hexachlorocyclohexane and transnonachlor had the highest impact. Most of the outcome was not explained by disturbances in the main cardiometabolic risk factors, ie, high body mass index, hypertension, lipid alteration, or diabetes.In this prospective nested case-control study, participants with higher exposures to organochlorines had an increased probability of experiencing a cardiovascular event, the major cause of death worldwide. Measures may be required to reduce these exposures.
Ziritaxestat and Lung Function in Idiopathic Pulmonary Fibrosis
Authors: Leticia Kawano-Dourado, Manuela Funke-Chambour, Athol U. Wells
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Propafenone versus amiodarone for supraventricular arrhythmias in septic shock: a randomised controlled trial
Authors: Martin Balik, Michal Maly, Tomas Brozek, Jan Rulisek, Michal Porizka, Robert Sachl, Michal Otahal, Petr Brestovansky, Eva Svobodova, Marek Flaksa, Zdenek Stach, Jan Horejsek, Lukas Volny, Ivana Jurisinova, Adam Novotny, Pavel Trachta, Jan Kunstyr, Petr Kopecky, Tomas Tencer, Jaroslav Pazout, Jan Belohlavek, Frantisek Duska, Adela Krajcova, Petr Waldauf
Journal: Intensive Care Medicine (2023)
Microbial stimulation of oxytocin release from the intestinal epithelium via secretin signaling
Authors: Heather A. Danhof, Jihwan Lee, Aanchal Thapa, Robert A. Britton, Sara C. Di Rienzi
Journal: Gut Microbes (2023)

Intestinal microbes impact the health of the intestine and organs distal to the gut. Limosilactobacillus reuteri is a human intestinal microbe that promotes normal gut transit, the anti-inflammatory immune system, wound healing, normal social behavior in mice, and prevents bone reabsorption. Oxytocin impacts these functions and oxytocin signaling is required for L. reuteri-mediated wound healing and social behavior; however, the events in the gut leading to oxytocin stimulation and beneficial effects are unknown. Here we report evolutionarily conserved oxytocin production in the intestinal epithelium through analysis of single-cell RNA-Seq datasets and imaging of human and mouse intestinal tissues. Moreover, human intestinal organoids produce oxytocin, demonstrating that the intestinal epithelium is sufficient to produce oxytocin. We find that L. reuteri facilitates oxytocin secretion from human intestinal tissue and human intestinal organoids. Finally, we demonstrate that stimulation of oxytocin secretion by L. reuteri is dependent on the gut hormone secretin, which is produced in enteroendocrine cells, while oxytocin itself is produced in enterocytes. Altogether, this work demonstrates that oxytocin is produced and secreted from enterocytes in the intestinal epithelium in response to secretin stimulated by L. reuteri. This work thereby identifies oxytocin as an intestinal hormone and provides mechanistic insight into avenues by which gut microbes promote host health.
Diagnosis and Treatment of Cirrhosis—Reply
Authors: Elliot B. Tapper, Neehar D. Parikh
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Fullerenols Mitigate Radiation‐Induced Myocardial Injury
Authors: Tingjun Zhang, Rendong He, Xuefeng Ding, Maoru Zhao, Chengyan Wang, Shuang Zhu, You Liao, Dongmei Wang, Hao Wang, Junsong Guo, Yaping Liu, Zhonghui Zhou, Zhanjun Gu, Houxiang Hu
Journal: Advanced Healthcare Materials (2023)

Abstract Radiation‐induced heart disease is a serious side effect of radiation therapy that can lead to severe consequences. However, effective and safe methods for their prevention and treatment are presently lacking. This study reports the crucial function of fullerenols in protecting cardiomyocytes from radiation injury. First, fullerenols are synthesized using a simple base‐catalyzed method. Next, the as‐prepared fullerenols are applied as an effective free radical scavenger and broad‐spectrum antioxidant to protect against X‐ray‐induced cardiomyocyte injury. Their ability to reduce apoptosis via the mitochondrial signaling pathway at the cellular level is then verified. Finally, it is observed in animal models that fullerenols accumulate in the heart and alleviate myocardial damage induced by X‐rays. This study represents a timely and essential analysis of the prevention and treatment of radiological myocardial injury, providing new insights into the applications of fullerenols for therapeutic strategies.
Additions to Funding/Support and Role of the Funder/Sponsor Sections
Authors: Toby Maher, Paul Ford, Marlies Wijsenbeek
Journal: JAMA (2023)

Kawano-Dourado and colleagues propose that poor adherence to antifibrotic drugs may explain the disease trajectories observed in the ISABELA placebo groups.The mean daily doses of pirfenidone were 2201 mg in ISABELA 1 and 2083 mg in ISABELA 2 1 ; the corresponding daily doses for nintedanib were 283 mg and 270 mg.These levels of exposure are comparable with those reported in the ASCEND trial 2 and in the INPULSIS trial. 3 Far from being concerning, as Kawano-Dourado and colleagues suggest, the data from the ISABELA trials 1 provide considerable reassurance.To be able to demonstrate that novel antifibrotic therapies slow the rate of decline of FVC, it is important that clinical trials are enriched for individuals with progressive disease.It seems that in the era of effective antifibrotic therapy, this enrichment is happening spontaneously; encouragingly, then, ongoing phase 3 trials should be sufficiently powered to show a benefit of novel therapies, if such a benefit exists.These findings highlight the critical importance of disseminating data from negative clinical trials.Although the participants in ISABELA 1 and 2 will undoubtedly have been disappointed by the outcome of the trials, 1 their involvement has taught the IPF community important lessons that will help optimize the design of future clinical trials.
Blood Transfusion and Brain Amyloidosis
Authors: Steven M. Greenberg
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Racial and Ethnic Differences in Receipt of Nonpharmacologic Care for Chronic Low Back Pain Among Medicare Beneficiaries With OUD
Authors: Fiona Bhondoekhan, Brandon D. L. Marshall, Theresa I. Shireman, Amal N. Trivedi, Jessica S. Merlin, Patience Moyo
Journal: JAMA Network Open (2023)

Nonpharmacologic treatments are important for managing chronic pain among persons with opioid use disorder (OUD), for whom opioid and other pharmacologic therapies may be particularly harmful. Racial and ethnic minority individuals with chronic pain and OUD are vulnerable to suboptimal pain management due to systemic inequities and structural racism, highlighting the need to understand their receipt of guideline-recommended nonpharmacologic pain therapies, including physical therapy (PT) and chiropractic care. To assess differences across racial and ethnic groups in receipt of PT or chiropractic care for chronic low back pain (CLBP) among persons with comorbid OUD. This retrospective cohort study used a 20% random sample of national Medicare administrative data from January 1, 2016, to December 31, 2018, to identify fee-for-service community-dwelling beneficiaries with a new episode of CLBP and comorbid OUD. Data were analyzed from March 1, 2022, to July 30, 2023. Race and ethnicity as a social construct, categorized as American Indian or Alaska Native, Asian or Pacific Islander, Black or African American, Hispanic, non-Hispanic White, and unknown or other. The main outcomes were receipt of PT or chiropractic care within 3 months of CLBP diagnosis. The time (in days) to receiving these treatments was also assessed. Among 69 362 Medicare beneficiaries analyzed, the median age was 60.0 years (IQR, 51.5-68.7 years) and 42 042 (60.6%) were female. A total of 745 beneficiaries (1.1%) were American Indian or Alaska Native; 444 (0.6%), Asian or Pacific Islander; 9822 (14.2%), Black or African American; 4124 (5.9%), Hispanic; 53 377 (77.0%); non-Hispanic White; and 850 (1.2%), other or unknown race. Of all beneficiaries, 7104 (10.2%) received any PT or chiropractic care 3 months after a new CLBP episode. After adjustment, Black or African American (adjusted odds ratio, 0.46; 95% CI, 0.39-0.55) and Hispanic (adjusted odds ratio, 0.54; 95% CI, 0.43-0.67) persons had lower odds of receiving chiropractic care within 3 months of CLBP diagnosis compared with non-Hispanic White persons. Median time to chiropractic care was longest for American Indian or Alaska Native (median, 8.5 days [IQR, 0-44.0 days]) and Black or African American (median, 7.0 days [IQR, 0-42.0 days]) persons and shortest for Asian or Pacific Islander persons (median, 0 days [IQR, 0-6.0 days]). No significant racial and ethnic differences were observed for PT. In this retrospective cohort study of Medicare beneficiaries with comorbid CLBP and OUD, receipt of PT and chiropractic care was low overall and lower across most racial and ethnic minority groups compared with non-Hispanic White persons. The findings underscore the need to address inequities in guideline-concordant pain management, particularly among Black or African American and Hispanic persons with OUD.
Funding Grants Added
Authors: Mytien Nguyen, Tonya Fancher, Dowin Boatright
Journal: JAMA (2023)

low-income students at a major disadvantage.Racially and ethnically underrepresented low-income students are 2 times more likely to leave medical school than their peers. 6Addressing barriers before and after medical school application will be critical to cultivate a diverse physician workforce.To address the inequities after medical school application, new directions in research will be necessary.First, future studies should examine additional measures of socioeconomic status to better understand the influence of wealth on a student's trajectory in medicine.These measures should extend beyond assessing income to include parental occupation and education and social and educational network metrics (such as the Child Opportunity Index).Second, a better understanding of the intersectionality between socioeconomic status, race, ethnicity, and the role of historical policies such as redlining and neighborhood segregation will be critical to quantify the full magnitude of structural barriers that minoritized low-income students encounter in their pursuit of medicine.Third, to create an environment in medicine where all individuals can thrive, tools need to be developed that can accurately measure the climate of equity and inclusion.Data from these assessments could be used to inform evidence-based interventions to promote equity and inclusion.Knowledge expansion in these areas will be critical to implement transformative change to create an equitable landscape for medical students and for the patients they will serve.
Clinical Correlates of Venetoclax-Based Combination Sensitivities to Augment Acute Myeloid Leukemia Therapy
Authors: Christopher A. Eide, Stephen E. Kurtz, Andy Kaempf, Nicola Long, Sunil Kumar Joshi, Tamilla Nechiporuk, Ariane Huang, Charles A. Dibb, Akosha Taylor, Daniel Bottomly, Shannon K. McWeeney, Jessica Minnier, Curtis A. Lachowiez, Jennifer N. Saultz, Ronan T. Swords, Anupriya Agarwal, Bill H. Chang, Brian J. Druker, Jeffrey W. Tyner
Journal: Blood Cancer Discovery (2023)

Abstract The BCL2 inhibitor venetoclax combined with the hypomethylating agent azacytidine shows significant clinical benefit in a subset of patients with acute myeloid leukemia (AML); however, resistance limits response and durability. We prospectively profiled the ex vivo activity of 25 venetoclax-inclusive combinations on primary AML patient samples to identify those with improved potency and synergy compared with venetoclax + azacytidine (Ven + azacytidine). Combination sensitivities correlated with tumor cell state to discern three patterns: primitive selectivity resembling Ven + azacytidine, monocytic selectivity, and broad efficacy independent of cell state. Incorporation of immunophenotype, mutation, and cytogenetic features further stratified combination sensitivity for distinct patient subtypes. We dissect the biology underlying the broad, cell state–independent efficacy for the combination of venetoclax plus the JAK1/2 inhibitor ruxolitinib. Together, these findings support opportunities for expanding the impact of venetoclax-based drug combinations in AML by leveraging clinical and molecular biomarkers associated with ex vivo responses. Significance: By mapping drug sensitivity data to clinical features and tumor cell state, we identify novel venetoclax combinations targeting patient subtypes who lack sensitivity to Ven + azacytidine. This provides a framework for a taxonomy of AML informed by readily available sets of clinical and genetic features obtained as part of standard care. See related commentary by Becker, p. 437 . This article is featured in Selected Articles from This Issue, p. 419
Lipid metabolic reprogramming in tumor microenvironment: from mechanisms to therapeutics
Authors: Hao-Ran Jin, Jin Wang, Zi-Jing Wang, Ming-Jia Xi, Bi-Han Xia, Kai Deng, Jin-Lin Yang
Journal: Journal of Hematology & Oncology (2023)

Abstract Lipid metabolic reprogramming is an emerging hallmark of cancer. In order to sustain uncontrolled proliferation and survive in unfavorable environments that lack oxygen and nutrients, tumor cells undergo metabolic transformations to exploit various ways of acquiring lipid and increasing lipid oxidation. In addition, stromal cells and immune cells in the tumor microenvironment also undergo lipid metabolic reprogramming, which further affects tumor functional phenotypes and immune responses. Given that lipid metabolism plays a critical role in supporting cancer progression and remodeling the tumor microenvironment, targeting the lipid metabolism pathway could provide a novel approach to cancer treatment. This review seeks to: (1) clarify the overall landscape and mechanisms of lipid metabolic reprogramming in cancer, (2) summarize the lipid metabolic landscapes within stromal cells and immune cells in the tumor microenvironment, and clarify their roles in tumor progression, and (3) summarize potential therapeutic targets for lipid metabolism, and highlight the potential for combining such approaches with other anti-tumor therapies to provide new therapeutic opportunities for cancer patients.
Medulloblastoma targeted therapy: From signaling pathways heterogeneity and current treatment dilemma to the recent advances in development of therapeutic strategies
Authors: Qiyue Wang, Xiaofei Xin, Qihao Dai, Mengjuan Sun, Jinhua Chen, Ebrahim Mostafavi, Yan Shen, Xueming Li
Journal: Pharmacology & Therapeutics (2023)
Single Center Experience with Voretigene Neparvovec Gene Augmentation Therapy in RPE65 Mutation–Associated Inherited Retinal Degeneration in a Clinical Setting
Authors: Birgit Lorenz, Sandrine H. Künzel, Markus N. Preising, Johanna P. Scholz, Petrus Chang, Frank G. Holz, Philipp Herrmann
Journal: Ophthalmology (2023)

To assess the impact of baseline data on psychophysical and morphological outcomes of subretinal voretigene neparvovec (VN) (Luxturna, Spark Therapeutics, Inc.) treatment.